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R D Harvey

Publications and source records attributed to R D Harvey.

47 records · Page 3Linked to original sources
PubMed1989

Voltage-dependent block of cardiac inward-rectifying potassium current by monovalent cations.

The inward-rectifying K+ current (IK1) in cat ventricular myocytes, like inward-rectifying K+ currents in many other preparations, exhibited a negative slope conductance region at hyperpolarized membrane potentials that was time-dependent. This was evident as an inactivation of inward current elicited by hyperpolarizing voltage-clamp pulses resulting in a negative slope region of the steady-state current-voltage relationship at potentials negative to -140 mV. Removing extracellular Na+ prevented the development of the negative slope in this voltage region, suggesting that Na+ can block IK1 channels in a time- and voltage-dependent manner. The time and voltage dependence of Cs+-induced block of IK1 was also examined. Cs+ blocked inward current in a manner similar to that of Na+, but the former was much more potent. The fraction of current blocked by Cs+ in the presence of Na+ was reduced in a time- and voltage-dependent manner, which suggested that these blocking ions compete for a common or at least similar site of action. In the absence of Na+, inactivation of IK1 could also be induced by both Cs+ and Li+. However, Li+ was less potent than Na+ in this respect. Calculation of the voltage sensitivity of current block by each of these ions suggests that the mechanism of block by each is similar.

Action Potentials↗
PubMed1989

Isoproterenol activates a chloride current, not the transient outward current, in rabbit ventricular myocytes.

The effects of beta-adrenergic stimulation on the Ca2(+)-insensitive transient outward current (Ito) in rabbit ventricular myocytes were examined. Exposure to isoproterenol (ISO; 1 microM) activated a time-dependent current at positive membrane potentials. To determine whether this ISO-induced current was associated with Ito, sensitivity to the K+ channel antagonist, 3,4-diaminopyridine (DAP; 200 microM) was compared before and after exposure to ISO. The DAP-sensitive current was not enhanced by ISO, suggesting that the ISO-induced current was not a component of Ito. Ito and the ISO-induced current could also be dissociated by changing the membrane holding potential. Positive holding potentials, which produced significant inactivation of Ito, had little effect on the ISO-induced membrane current. Furthermore, the ISO-induced current could be observed when K+ was replaced by Cs+. The reversal potential of the ISO-induced current agreed with the predicted Cl- equilibrium potential, and exposure to Cl(-)-free extracellular solutions eliminated the response to ISO. Therefore, we conclude that ISO does not directly activate Ito in rabbit ventricular myocytes, but instead, activates a time-independent chloride current (ICl) similar to that recently described in guinea pig ventricular myocytes and shown to be regulated by adenylate cyclase (R. D. Harvey and J. R. Hume. Science Wash. DC 244: 983-985, 1989).

4-Aminopyridine↗
PubMed1989

Autonomic regulation of delayed rectifier K+ current in mammalian heart involves G proteins.

The role of adrenergic and cholinergic stimulation in regulating the delayed outward K+ current (IK) was examined by using isolated guinea pig ventricular myocytes. Isoproterenol (ISO) stimulated IK in a reversible manner. Similar effects were seen by directly stimulating adenylate cyclase with forskolin (FSK). The responses to ISO and FSK were reversed by concurrent application of acetylcholine (ACh), but ACh alone did not affect IK. When a nonhydrolyzable analogue of guanosine 5'-triphosphate was introduced intracellularly, in the presence of extracellular ISO, IK was irreversibly stimulated. In cells pretreated with pertussis toxin the ACh response was blocked. These results suggest that autonomic regulation of IK is similar to that of the Ca2+ current and involves guanine nucleotide-binding proteins. This has important implications with respect to autonomic control of action potential duration and pacemaker activity in the heart.

Acetylcholine↗
PubMed1989

Diagnostic problems caused by spurious elevation of thyrotrophin measured by sensitive assay.

Thyrotrophin measured by the Amerwell immunoradiometric assay was found to be falsely elevated, causing potential diagnostic confusion in hypothyroid, euthyroid and hyperthyroid individuals. Non-specific antibodies in patients' sera may be responsible, by cross-linking the mouse monoclonal antibodies of the assay. Interference was overcome in the sera from these patients by addition of mouse serum (20 microliters per ml test serum) over and above that already incorporated in the kit. Problems with spuriously elevated thyrotrophin levels are not confined to one manufacturer's kit and can cause diagnostic confusion in several situations.

Adult↗
PubMed1988

Characterization of the inward-rectifying potassium current in cat ventricular myocytes.

Whole-cell membrane currents were measured in isolated cat ventricular myocytes using a suction-electrode voltage-clamp technique. An inward-rectifying current was identified that exhibited a time-dependent activation. The peak current appeared to have a linear voltage dependence at membrane potentials negative to the reversal potential. Inward current was sensitive to K channel blockers. In addition, varying the extracellular K+ concentration caused changes in the reversal potential and slope conductance expected for a K+ current. The voltage dependence of the chord conductance exhibited a sigmoidal relationship, increasing at more negative membrane potentials. Increasing the extracellular K+ concentration increased the maximal level of conductance and caused a shift in the relationship that was directly proportional to the change in reversal potential. Activation of the current followed a monoexponential time course, and the time constant of activation exhibited a monoexponential dependence on membrane potential. Increasing the extracellular K+ concentration caused a shift of this relationship that was directly proportional to the change in reversal potential. Inactivation of inward current became evident at more negative potentials, resulting in a negative slope region of the steady state current-voltage relationship between -140 and -180 mV. Steady state inactivation exhibited a sigmoidal voltage dependence, and recovery from inactivation followed a monoexponential time course. Removing extracellular Na+ caused a decrease in the slope of the steady state current-voltage relationship at potentials negative to -140 mV, as well as a decrease of the conductance of inward current. It was concluded that this current was IK1, the inward-rectifying K+ current found in multicellular cardiac preparations. The K+ and voltage sensitivity of IK1 activation resembled that found for the inward-rectifying K+ currents in frog skeletal muscle and various egg cell preparations. Inactivation of IK1 in isolated ventricular myocytes was viewed as being the result of two processes: the first involves a voltage-dependent change in conductance; the second involves depletion of K+ from extracellular spaces. The voltage-dependent component of inactivation was associated with the presence of extracellular Na+.

Animals↗
PubMed1988

5-(N,N-dimethyl)amiloride-sensitive Na-Li exchange in isolated specimens of human atrium.

To examine if a transmembrane Na-Li exchange similar to that reported to occur in human blood cells can be demonstrated in the heart, we incubated specimens of human atrium in cold (2-3 degrees C) Li-Tyrode's solution. The Li-loaded, Na-depleted specimens were then transferred to warm (30 degrees C) Na-Tyrode's solution. After transfer the membrane potential hyperpolarized to a level more negative than the equilibrium potential for K+. The hyperpolarization was inhibited by acetylstrophanthidin or K+-free solution indicating that it was due to current produced by the Na, K-pump responding to a Na load. This suggested that intracellular Li+ had been exchanged for Na+. The hyperpolarization was abolished by 10 microM 5-(N,N-dimethyl)amiloride while 10 microM bumetanide had no effect, findings that are consistent with the notion that the exchange of intracellular Li+ for extracellular Na+ occurs via an operational mode of the Na-H exchanger rather than being mediated through a mechanism involving the Na/K/2Cl cotransporter.

Amiloride↗
PubMedDate not supplied

Granulocyte colony-stimulating factor use in cancer patients.

OBJECTIVE: To conduct a retrospective drug utilization evaluation comparing the use of granulocyte colony-stimulating factor (G-CSF) at a university medical center with the American Society of Clinical Oncology (ASCO) CSFs Practice Guidelines. METHODS: Patients who received G-CSF from June 1, 1996, to December 31, 1996, were identified through the pharmacy computer system and the medical records were reviewed for a randomly selected sample of 26% of the 289 patients identified. Outpatient, inpatient, and electronic medical records were reviewed for the indication, dosage, day of initiation, day of discontinuation, and absolute neutrophil count (ANC) monitoring plan for each course of G-CSF; these records were subsequently compared with the ASCO guidelines. RESULTS: The use of G-CSF after chemotherapy was evaluated in 51 patients who received a total of 182 courses of G-CSF. The goal of chemotherapy was curative in 61% of courses. Sixty-five percent of G-CSF courses were prescribed for primary prophylaxis. Of these, 74% followed chemotherapy in patients with an expected incidence of febrile neutropenia > or =40% or followed chemotherapy in patients with compromised marrow reserve secondary to extensive prior therapy or in patients older than 60 years. Most of the G-CSF courses (75%) were rounded to the nearest vial size. The areas of greatest departure from the ASCO guidelines included aspects of initiation and discontinuation of G-CSF courses and inadequate documentation of ANC recovery. CONCLUSIONS: These results demonstrate a number of specific opportunities for oncology pharmacists to improve the use of G-CSF in patients receiving chemotherapy. Recommendations were made to the pharmacy and therapeutics committee and medical oncologists to improve compliance with the ASCO guidelines.

Aged↗